Flow Cytometric Measurement of Aneuploid DNA Content Correlates with High S-Phase Fraction and Poor Prognosis in Patients with Non-Small-Cell Lung Cancer

Cellular DNA content (ploidy) and proliferation activity (e.g., S-phase fraction) measured by flow cytometry have been usually related to the biologic aggressiveness of various neoplasms. In this study, these parameters were analyzed in paraffin-embedded tumor specimens from 43 cases of resected non-small-cell lung cancer (NSCLC). Additionally, the correlation of them with both prognosis and a variety of clinic-pathological features were investigated. The stage and the appearance of both local recurrence and metastasis were related to overall survival of patients. Twenty-two tumors (51.2%) had a diploid DNA distribution, while 21 were aneuploid (48.8%). The mean of aneuploidy was 1.6% ± 0.3%. A correlation was found between ploidy and survival as well as with the appearance of local recurrence and/or metastasis. The mean values of S-phase fraction of diploid and aneuploid tumors were 16.7 ± 11.3% and 32.9 ± 12.1%, respectively, which were significantly different ( ). Similar results were obtained analyzing the proliferation index (sum of cells in S and G2/M phases of cell cycle) ( ). However, no correlation between these parameters and both overall survival of patients and clinicopathological features was observed. Our results could suggest the potential use of ploidy analysis as a useful complement of TNM stage in NSCLC. 1. Introduction Lung cancer is one of the most frequently occurring neoplasms and is the leading cause of death by cancer worldwide [1]. There are two main variants of the disease, non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, NSCLC represents more than 80% of all lung carcinomas [2]. Usually patients with NSCLC have a poor prognosis because most of them present with advanced or metastatic diseases at the time of diagnosis. It has been estimated that only 10–15% of the patients will ultimately be cured [3]. In patients with NSCLC, some genetic and regulatory aberrations have been considered responsible for the tumor survival advantage. For that reason, several tumor markers, clinic-pathological indicators, and genetic alterations have been assessed in NSCLC for identifying patients with a poor prognosis and for a better guide of treatment strategy [4]. It is known that the development of malignant neoplasm occurs through a multistep genetic evolution process which often is accompanied by chromosome instability [5, 6]. Chromosomal instability of tumors leads to cell clones and to numerical and structural chromosome abnormalities. These changes in the number of whole chromosomes (aneuploidy) can stimulate